Pharmacogenetics

Question 1

1. Define and distinguish between pharmacogenetics and pharmacogenomics.

Answer 1

Pharamacogenetics: study of differences in drug response due to allelic variation in genes affecting drug metabolism, efficacy, toxicity
-variable response due to individual gene(s)
how does an individual gene affect drug therapy?

Pharmacogenemoics: the genetic appraoch to pharmacogenetics, concerned with the assessment of common genetic variants in the aggregate for their impact on the outcome of drug therapy

• basically sum shit together, how does it affect drug therapy
• variable response due to multiple loci across the genome

Question 2

2. Explain the two major physiologic response to drugs, pharmacokinetics and pharmacodynamics, and briefly contrast Phase I and Phase II drug metabolism steps.

Answer 2

after drug is taken, it must:

a) reach its target(s)
b) exert its effect
c) do the above before being inactivated/eliminated

pharmacokinetics: describes absorption, distribution, metabolism and excreation of drugs (ADME is the acronym)

Pharmacodynamics: describes the relationship between the concentration of a drug at its site of activation and the observed biological effects

Drug Metabolism:
Phase 1: polar group added (exposed) -> solubilze
Phase 2: conjugation reaction (sugar/acetyl group)-> detoxify

Question 3

3. Explain the central role of the CYP450 enzyme system in drug metabolism.

Answer 3

Gene products active in liver and intestinal epithelium
3 main families (CYP1, CYP2, CYP3)
CYP3A4-> 40% of all common drugs
Most CYPs function to inactivate drugs, but rarely function for activation (Codeine-> morphine and CYP2D6 is classic example)

Basically mutations in this affect rate of drug metabolism (causing it to be either, poor,normal or super fast which affects the effectiveness of drugs and when various dosages should be given)
-standard possible mutations like frameshifts, deletions, splicing, nonsense, missense

Question 4

4. Recognize and understand key specific pharmacogenetic examples from the text and this handout.

Answer 4

CYP3A: Cyclosporine, ketoconazole, rifampin, grapefruit juice( more relevance of environmental factors than specific genotypes)
CYP2D6: Codeine-> morphine exmaple (one of the few cases of activation)
CYP2C9+VKORC1: warfarin
NAT: Isonazid
TPMT:(6-mercaptopurine/6-thigaunine and childhood ALL)

Question 5

5. Recognize the truism of the axiom Variety is the spice of life!

Answer 5

yeah just that